Case 20:

Discussant: DANIEL HALLER, MD

Case Description:

A 62-year-old woman was diagnosed three years ago with a T3N1 low rectal cancer and received neoadjuvant chemoradiation therapy followed by resection with permanent colostomy and four additional cycles of postoperative 5-FU/LV. She now presents with surveillance CT evidence of five unique bilobar hepatic metastases, including segments II, VI, VII and VIII. Of note, the lesion in segment VIII appeared flush against a major aortic branch vessel. She received six cycles of FOLFOX/bevacizumab. On completion of therapy, her disease was restaged and was deemed resectable. She underwent an extended right hepatectomy but intraoperative ultrasound identified a metastasis in segment III of the left lobe, in addition to the two known lesions in segment II, making complete resection with adequate liver reserve impossible. She was placed on intercurrent capecitabine and is scheduled to undergo a second stage resection after evidence of postoperative liver regeneration.

Case Discussion:

DR HALLER: This 62-year-old woman presented as a challenging case. I believe most institutions would never even have considered a potentially curative approach for this patient. Three years ago she underwent preoperative 5-FU and radiation therapy for T3/N1 rectal cancer, a pretty standard approach. She required a colostomy, because the tumor was low.

After surgery, she received four additional cycles of 5-FU, so the treatment she received was similar to that administered in the German preoperative trial. Post-treatment surveillance consisted of measuring CEA levels every three months and CT scans of the abdomen and the pelvis every six months.

Three years after her presentation, a CT scan showed a three-centimeter lesion in segment VIII of the liver, abutting the major arteries from the aorta, and an experienced radiologist could not see a normal rim of tissue adjacent to the vessels. Also, in the right lobe there was a 4-cm lesion in segment VI and a 2-cm lesion in segment VII. In the left lobe, two separate 3- to 4-cm lesions in segment II. This was clearly a complicated case with a total of five hepatic lesions involving two lobes and at least one lesion was not primarily resectable.

This case required a lot of thought and a good deal of radiologic intervention. A PET scan showed no other lesions. An experienced surgeon felt the patient was not resectable based on the lesion in segment VIII, so she received six cycles of FOLFOX and bevacizumab, which is de facto the standard first-line approach for most institutions and practices in the United States.

The story could have ended there in many institutions, because the patient was considered to have unresectable, incurable metastatic disease and chemotherapy would have been palliative. However, we did not want to totally eliminate the possibility of surgery, so we restaged her disease after six cycles. The tumors had all shrunk by approximately 30 percent, and it appeared the resection was now possible in segment VIII based on a rim of fairly normal-looking tissue.

The patient underwent an extended right hepatectomy, removing the lesions in segments VIII, VI and VII — it was an R0 resection. An intraoperative ultrasound showed an additional small metastasis in segment III, and radiofrequency ablation (RFA) was not considered feasible.

A number of different approaches were discussed. What if RFA were feasible? Could she have had a right extended hepatectomy? That would have taken approximately 70 percent of the liver and would be pushing the boundaries of how much normal liver volume one can leave behind. Could we perform a RFA of the three lesions? In general, most people consider RFA to be a second-class citizen in terms of curability, because you may not know the extent of your resection margin. We decided that RFA was not the best approach for this patient. It didn’t make sense to perform an extended right hepatectomy and then conduct a lesser procedure in the left lobe simply to accomplish it all in one trip to the operating room.

Instead, we planned to perform a two-stage procedure. We didn’t consider portal vein embolization, because frankly our surgeons don’t perform them. We have a reasonably high volume, but we don’t have that high a volume. While I haven’t done a formal poll, I’ll bet no more than five or 10 institutions in the United States perform that procedure and have enough experience doing it. Also, in this case, we didn’t feel it was necessary. We felt we could rely on natural regeneration.

The patient received no additional cycles of her chemotherapy regimen at that point as we wanted to avoid hepatotoxicity during liver regeneration and before a planned liver resection. She received single-agent capecitabine and was observed.

We didn’t administer bevacizumab because we’re not entirely sure of what effect it might have on post-resection regeneration. She had a response, and now we’re maintaining it with less toxic therapy. This is the OPTIMOX approach of treating with six cycles of combination chemotherapy with a biologic, and then maintaining the patient on the least toxic drug, a fluoropyrimidine.

Further resection of the liver was planned for when the patient was fully recovered and when the surgeons felt comfortable enough to remove the lesions in the left lobe. Within three to four months, most patients will have enough regrowth of liver to allow for further surgery. The size of the tumor is also an important consideration. This patient has relatively small volume in the left lobe, so it won’t require a huge amount of surgery. They’ll probably be able to get by with three wedge resections, rather than a formal left, so we’ll see.